Abstract
Background: Pulmonary arterial hypertension (PAH) is a gradually worsening disease with an unfavourable outcome. Iron deficiency seemingly has an essential part in the progress of the disease, as its relationship with disease severity and mortality from any cause has been demonstrated. While suitable substitution therapy may be advantageous (analogous to patients with left heart failure), iron absorption from the gut is suppressed in PAH by hepcidin, the master regulator of iron metabolism. We therefore examined the potential benefit of intravenous iron administration in iron deficient PAH patients. Methods: A single infusion of ≤ 1000 mg ferric carboxymaltose was administered to 20 iron deficient patients with PAH (NYHA-FC II/III) on stable background PAH treatment. These patients were assessed at baseline and two months after intervention. The 6-minute-walking distance (6MWD) was measured to assess exercise capacity and the SF-36 questionnaire (100 point scale) was used to evaluate quality of life. The results were compared with 20 matched patients with stable disease who were not given iron infusions. Results: In patients with iron deficiency, iron infusion led to a markedly enhanced iron status (serum iron 5.7±2.0 to 11.1±5.0 μmol/l, ferritin 29.3±28.2 to 145.2±113.7 μg/dl, transferrin saturation 7.5±3.1 to 19.3±10.2%, all p<0.001), whereas no differences in iron status were seen in the control group. Ferric carboxymaltose lead to a mean increase in the 6MWD of 37.8 m in patients with iron deficiency compared with controls (95% CL -40.8, 116.4 m; mean increase from 346.5±126.4 to 374.0±113.9 m; p=0.003), and quality of life improved, too (raise of the SF-36 score from 44.3±16.5 to 50.6±15.9; p=0.01). There were only slight adverse effects. Expectedly, no significant differences in exercise capacity were found in the control group not receiving iron infusions (6MWD 389.9±113.1 vs. 379.6±117.3 m; n.s.). Conclusions: Our study shows that intravenous iron loading with ferric carboxymaltose is well tolerated in iron deficienct PAH patients and has significant benefit on exercise capacity and quality of life in addition to background PAH therapies. These benefits warrant additional studies to assess the value of iron as supplementary therapy for an extended population of PAH patients.
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